CD44 is expressed on a wide variety of normal cells including cells of the central nervous system (CNS). The expression of CD44s in the CNS is localized to glial tissue. Interestingly, a majority of intrinsic brain tumors are derived from glial tissue. In addition, over-expression of CD44s has been detected in the highly malignant glioblastoma multiforme. These finding have prompted the investigation of whether CD44s plays an important role in neoplastic development in the CNS. The highly invasive character of glioblastomas intraneurally may be different from those systemic tumors which metastasize to the brain, a phenomenon in which CD44 variants have been implicated in playing a role. However, the inability of glioblastomas to metastasize extraneurally may be a consequence of the fact that they do not express CD44 variants. We propose to investigate these questions by 1) investigating the role CD44 plays in human glioma invasion and metastatic brain tumor growth by ablating its expression using ribozyme directed cleavage and 2) introducing the expression of CD44 variants, by transfection with CD44 variant containing constructs, into human brain tumor cells to determine if an alteration in tumor growth and invasive proclivity results.